text:
You missed it This great deal for Puerto Vallarta is over. But don't despair, we've got more great deals every day.
Related Deals That You May Like
Caña Cuban Parlor & Cafe
Cuban Food & Salsa Dancing Package
Napa / Sonoma$120$59.99
Morimoto Napa
6-Course Omakase Lunch for 1 or 2 with Bubbly
Napa / Sonoma$120$75
Blue Water Seafood and Crab
3, 4, 5, or 6-Pound Seafood Bucket with Drinks
Napa / Sonoma$69$41.99
The Mountain Winery
Wine Tasting for 2 with a Take-Home Bottle
Napa / Sonoma$65$39
Puerto Vallarta
$30 to Spend on Mexican Cuisine and Drinks
76% recommendedin LivingSocial customer ratings
Amidst a festive atmosphere of live mariachi music and cheerful décor, you'll find adventurous dining options such as the Mexican-style goat shank plate; as well as old favorites like chorizo burritos, chicken enchiladas, beef tostadas, and more:
• $15 for $30 to spend on food and drink
• To start, try the Nachos Idaho topped with potato skins, beef, and melted cheddar
• Follow up with chicken mole, prawn carnitas, or an enchilada and chile relleno
"This place has wonderful Mexican food! The service is top notch, with friendly waiters who are also efficient. On some nights they have live music... and the chips are always hot and fresh, with good salsa." - Judy's Book Reviewer
PAID VALUE EXPIRES ON July 29, 2021
PROMOTIONAL VALUE EXPIRES ON May 12, 2014
Buy this Deal with confidence, because it's covered by the LivingSocial Good Deal Guarantee up to the Voucher Expiration DateSee Details »
the fine print
- Limit 1 per customer, up to 3 additional as gifts
- Limit 1 per table per visit
- Reservations required and subject to availability
- Merchant cancellation/re-scheduling policy of 24 hours applies; voucher subject to forfeiture
- Valid only for dine-in
- Discount apportioned among all items purchased. No item provided free
- Entire value must be used in a single visit
- Other conditions apply
special delivery
shop unique gifts and deliver them with style
easy, flexible delivery
print it out, email it now, or schedule it for a later date--it's up to you
personalized email
Emailing your gift? Write a message, select a theme, and hit send. The price you paid will not be displayed in the email.
special printed voucher
Delivering the gift in person? Choose a theme, print it out, and pass it along to that special someone. It's that simple.
Deal Fine Print
Limit 1 per customer, up to 3 additional as gifts
• Limit 1 per table per visit
• Reservations required and subject to availability
• Merchant cancellation/re-scheduling policy of 24 hours applies; voucher subject to forfeiture
• Valid only for dine-in
• Discount apportioned among all items purchased. No item provided free
• Entire value must be used in a single visit
• PAID VALUE EXPIRES ON July 29, 2021
• PROMOTIONAL VALUE EXPIRES ON May 12, 2014
• Cannot be combined with any other offer or promotion
• Tax and gratuity are not included
• Merchant is responsible for the quality of the products or services provided to you at redemption
• LivingSocial Terms and Conditions - https://www.livingsocial.com/terms


text:
Sustainable Investing
Renewable Energy Is a 'Bubble,' Says Financier
Per Wimmer on why green energy faces many challenges
Sustainable investing and clean energy are hot topics, but one Danish financier is warning that people might be getting carried away.
Per Wimmer, a former Goldman Sachs banker and the founder of Wimmer Financial LLP, a London-based corporate-advisory firm specializing in natural resources, foresees a "green bubble" that could have similar consequences to the dot-com and housing bubbles.
The Wall Street Journal asked the...

subset: commoncrawl


text:
KANSAS CITY, Mo. -- Ivan Dominguez of Cuba fought off cramps
and a hill on the final stretch to break out of a tight group of
riders to win the first stage of the inaugural Tour of Missouri on
Dominguez, riding for Toyota-United, was without any team
members to help as he took the lead with about 300 yards to go and
finished in 3:05:37.
Each Bell of Symmetries Cycling team was second, followed by
Kyle Wamsley of Navigators Insurance Cycling.
Tour de France champion Alberto Contador of Discovery Channel
was 85th among the team of international riders who made the
85-mile circuit beginning and ending in Kansas City's Country Club
An estimated 40,000 spectators lined the streets and highways as
the riders made their way through downtown Kansas City, along the
Missouri River and through small towns in the sometimes-hilly
country of northwest Missouri. Weather for Missouri's first foray
into international racing was perfect -- low winds, blue skies and
warm temperatures in the mid-80s.
Dominguez's average winning speed was 27.557 mph.
"I was not expecting to see that climb there," Dominguez said.
"It put my legs under a little bit of pressure. I started getting
tired. I looked, and thought, 'I'm going to go and see what
"And I started going and passing guys like they were standing
there. I was like, 'Wow! this is great.'"
The six-day, 600-mile race started on Kansas City's Country Club
Plaza, where fans applauded cycling heavyweights including Contador
and American champion Levi Leipheimer, who had to pause for several
minutes early in the race to replace a chain.
For their Discovery Channel team that has dominated
international cycling for almost a decade and won eight of nine
Tour de France titles, it will be the last race on American soil.
Discovery will soon disband, and other teams are eager to
welcome its riders.
Organizers and state officials must have been pleased with the
reception the riders got along the way. In every town, spectators
lined the roads, many holding signs greeting the riders and
thanking them for coming to Missouri. In one town, excited
youngsters came spilling out of an elementary school just as the
pack sped past.
Dominguez said he thought he was finished when his legs began
"Coming to that back stretch, I thought, 'This climb is going
to put a lot of guys in trouble,"' he said. "I was one of those
guys. It was good we had the downhill."
His victory had been predicted by many cycling fans.
"Before the race I got a lot of people came to me. They said,
'We're going to put some money on you.' I said don't put too much.
I was not expecting to win this race today. I was not expecting to
see that climb in the end."
The race, touted by the governor's office as the largest
sporting event in the history of the state, will end on Sunday in
St. Louis.
The race will pass through 20 counties and about 50 cities and
towns, continuing Wednesday with a leg from Clinton to Springfield.
On Sunday, the race will conclude with a circuit race in St. Louis
in what will be one of the city's most crowded sports days.
Also Sunday, the St. Louis Cardinals are hosting the rival
Chicago Cubs and the St. Louis Rams are facing the San Francisco
49ers. That night, the NHL's St. Louis Blues will be playing their
first home exhibition game.


text:
Chateau De Vauloge, Le Mans - Sarthe (department)
- Free buffet breakfast, free WiFi, and free parking
Main amenities
- 5 smoke-free guestrooms
- Seasonal outdoor pool
- Daily housekeeping
- Garden
- Library
- Lobby fireplace
- Meeting rooms
- Multilingual staff
- Limited hour front desk
- Tour/ticket assistance
- TV in a common area
What's around
- Church of St Peter - St Paul (13.9 mi / 22.3 km)
- Claude Chappe Museum (13.9 mi / 22.3 km)
- St Peter's Abbey of Solesmes (14.4 mi / 23.2 km)
- Abbey of St Cecile (14.5 mi / 23.3 km)
- Lake Brulon (14.8 mi / 23.8 km)
We needed somewhere to stop off on our way to Le Havre coming from Angouleme. It was…
Fantastic !
Chateau De Vauloge, Le Mans - Sarthe (department)
Hotel Info: 866-539-8117from $236
- Double Room
- Suite, 2 Double Beds
- Suite
Also popular with travelers from the USA
At a glance
Key facts
Hotel size
- This hotel has 5 rooms
- This hotel is arranged over 2 floors
- Check-in time 3 PM-7 PM
- Check-out time is 11 AM
Required at check in
- Credit card or cash deposit required
- Government-issued photo ID required
Travelling with others
- One child (2 years old and younger) stays free when occupying the parent or guardian's room, using existing bedding
- Pets not allowed
- Free WiFi in public areas
- Free WiFi in rooms
- Free self parking
Other information
- Smoke-free property
Nearby One Star Le Mans - Sarthe (department) hotels
In the hotel
- Free buffet breakfast daily
- Outdoor seasonal pool
- Pool sun loungers
- Bicycle rentals nearby
- Golf lessons available nearby
- Golfing nearby
- Hiking/biking trails nearby
- Kayaking nearby
- Mountain biking nearby
- Pool umbrellas
- Meeting rooms
- Front desk (limited hours)
- Tours/ticket assistance
- Multilingual staff
- Number of buildings/towers - 1
- Garden
- Library
- Fireplace in lobby
- Television in common areas
In the room
- Coffee/tea maker
- Bathrobes
- Slippers
- Egyptian-cotton sheets
- Pillowtop mattress
- Individually decorated
- Individually furnished
- Private bathroom
- Bathtub or shower
- Bidet
- Free toiletries
- Hair dryer
- Desk
- Free WiFi
- Free bottled water
- Daily housekeeping
Top Le Mans - Sarthe (department) hotels
Recently reviewed hotels in Le Mans - Sarthe (department)
- Hôtel Concordia Le Mans Centre gareFrom
"i don't normally stay in business hotels, but this was the closest to the train station/tram."Jun 6, 2016
- Inter-hotel AlizeaFrom
"Comfortable room and beds and a walk out patio into nice green areas with great view of the beautiful surroundings. Conveniently located near the highways and shopping areas,…"Jul 26, 2015
- Best Western Premier Le Mans Country ClubFrom
"Very relaxing and pleasant place to stay."Jul 20, 2015
- B&B Hôtel LE MANS Nord (1)From
Chateau De Vauloge, Le Mans - Sarthe (department)'s small print
Also known as
- Chateau Vauloge Ferce-sur-Sarthe
- Chateau Vauloge Hotel
- Chateau Vauloge Hotel Ferce-sur-Sarthe
- Chateau De Vauloge Hotel Ferce-Sur-Sarthe
- Chateau De Vauloge Sarthe, France
- Chateau Vauloge House Ferce-sur-Sarthe
- Chateau Vauloge
- Chateau De Vauloge Sarthe France
This property does not have elevators.
Reservations are required for massage services and can be made by contacting the property before arrival at the number on the booking confirmation.
Optional extras
Rollaway beds are available for EUR 70.00 per night
Cribs/Infant beds are available for EUR 40 per day
We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.
Is the description of this hotel not correct? Tell us


text:
Thomiesena Cunningham
Published: Tuesday, August 8, 2006 at 3:15 a.m.
Last Modified: Tuesday, August 8, 2006 at 12:00 a.m.
RANDALLSTOWN, MD-- Ms. Thomiesena Cunningham, 84, of 4262 Mary Ridge Drive, Randallstown, MD, passed away on August 5, 2006.
Survivors include one daughter, Ms. Gladys Cunningham of Randallstown, MD; one sister-in-law, Mrs. Ellen J. Cunningham of Cincinnati, OH; five nieces, Ms. Mildred Smith, Ms. Loualgia Palmer, Ms. Dorothy (Wesley) Smith, all of Spartanburg, SC, Ms. Marilyn Anderson of Cincinnati, OH, Ms. Rita Buck-Crockett of Florida; and one nephew, Mr. Herman Crockett of Texas.
Funeral service will be held on Wednesday morning at 11:00 AM at the Allen View United Methodist Church, Reidville, SC. Rev. Alfred Wright will officiate. Burial will be in the church cemetery.
The family will receive friends on Wednesday at 10:00 AM prior to the service.
J. W. Woodward
Funeral Home
Paid Funeral Notice
Reader comments posted to this article may be published in our print edition. All rights reserved. This copyrighted material may not be re-published without permission. Links are encouraged.
Comments are currently unavailable on this article


text:
Holly Benson's file
Republican from Florida
Holly Benson is a former secretary for the Agency for Health Care Administration. She campaigned to be Florida Attorney General and was defeated in the Republican primary on Aug. 24, 2010.
Benson's statements by ruling
Click on the ruling to see all of Benson's statements for that ruling.
- True0(0)
- Mostly True2 (%)(2)
- Half True0(0)
- Mostly False0(0)
- False0(0)
- Pants on Fire0(0)


text:
What's the best way to eat a bag of jelly beans?
Many people open the bag and eat all the candy, no matter what flavor each piece is. Others pick through the collection. They might say "I don't like the orange ones." Or maybe they just care for the lemon ones. There are different kinds of jelly beans in the mixture and people will eat what they want and get rid of the rest.
Heterogeneous Mixtures
A heterogeneous mixture is a mixture in which the composition is not uniform throughout the mixture. Vegetable soup is a heterogeneous mixture. Any given spoonful of soup will contain varying amounts of the different vegetables and other components of the soup.
A phase is any part of a sample that has a uniform composition and properties. By definition, a pure substance or a homogeneous mixture consists of a single phase. A heterogeneous mixture consists of two or more phases. When oil and water are combined, they do not mix evenly, but instead form two separate layers. Each of the layers is called a phase.
In the vegetable soup example, one phase would be the liquid soup itself. This phase has vitamins, minerals, and other components dissolved in the water. This phase would be homogeneous. The carrots, peas, corn, or other vegetables represent other phases of the soup. The various vegetables are not mixed evenly mixed in the soup, but are spread around at random.
There are a large number of heterogeneous mixtures around us. Soil is composed of a variety of substances and is often of different composition depending on the sample taken. One shovel may come up with dirt and grass while the next shovel could contain an earthworm.
Smog is another example of a heterogeneous mixture. This murky collection of pollutants can be a mixture of water and contaminants from burning gasoline or plastics mixed with nitric oxide derivatives and ozone. You can see that the smog distribution in the air illustrate below is not evenly spread out, but varies from one part of the atmosphere to another.
- A heterogeneous mixture is a mixture in which the composition is not uniform throughout the mixture.
- A phase is a separate layer in a heterogeneous mixture.
Explore More
Use the link below to answer the following questions:
- Heterogeneous Mixture Properties and Examples at https://blog.udemy.com/heterogeneous-mixture/.
- What is a heterogeneous mixture?
- Why is a bucket of sand and water heterogeneous?
- Describe the physical separation of a heterogeneous mixture.
- What is an emulsion?
- What is an aerosol?
- Why is pizza heterogeneous?
- Define a heterogeneous mixture.
- Why is vegetable soup a heterogeneous mixture?
- How many phases are in a heterogeneous mixture?


text:
We're sorry, but chat isn't available at the moment. Agents may be helping other customers or Live Chat may be closed.
Please check back soon.
6 a.m. to 6:30 p.m. PT
7 days a week
Available Now Coming Apr 05, 2010
Nintendo DS
Time to clean up the neighborhood! Move the player to the left and
the right, hitting the moles that appear.
Nintendo first began releasing the Game & Watch series in 1980. This collection of games was available on portable LCD devices, and each title featured a game and a clock. Each Game & Watch title features two modes of play: GAME A (normal difficulty) and GAME B (more advanced play). While some controls have been changed in the DSiWare version to better suit the Nintendo DSi system, the appearance of the game itself has not been altered.
Time to clean up the neighborhood! Move the player to the left and the right, and hit the moles that pop out of holes in the ground. Moles appear from four holes in GAME A and from five holes in GAME B. The moles in GAME B move faster than those in GAME A, and they also appear more frequently. Earn one point for each mole hit, or receive a mistake icon for each missed hit. Receive three mistake icons, and it's game over!
* If eligible for a Just for You offer, the final price reflects the combined Sale and Just for You offers. The Just for You offer is discounted from the sale price.
A Nintendo Account with a linked Nintendo Network ID is required to purchase games through www.nintendo.com. To purchase a game, complete the following steps:
For additional information about this process, please click here.
Yes. You will need a Nintendo Account with a linked Nintendo Network ID to purchase games through www.nintendo.com. The games you buy will be automatically downloaded to the system (Wii U and / or Nintendo 3DS family) that is associated with your Nintendo Network ID.
You'll need a Wii U or Nintendo 3DS family system (registered for use in the U.S. or Canada), Nintendo Network ID*, Internet connection, and Nintendo eShop access to download the game once you've purchased it.
For help downloading a game, click here.
(* You'll need a Nintendo Network ID to download the game, but you won't need one to play the game once it has been downloaded.)
Yes. As long as you have signed up for My Nintendo before you purchase the game, your game will qualify for My Nintendo Points. My Nintendo Points are automatically awarded to the Nintendo Account that was used to purchase the game. (Please note that DLC items, passes, and themes do not qualify for My Nintendo Points.)
To see your My Nintendo points balance:
Once you're signed in, you can review your My Nintendo points balance and history, check out the latest My Nintendo rewards, and view active missions you can complete to earn My Nintendo points.
For additional help with My Nintendo, please visit our support site.
All sales are final. Please be sure that you meet all of these download requirements for your game before you place your order.
For additional information, please see the Purchase Terms.


text:
|Publication number
|Publication type
|Application number
|Publication date
|Nov 26, 1996
|Filing date
|Nov 14, 1994
|Priority date
|Feb 12, 1990
|Fee status
|Publication number
|Carine Capiau, Jean Petre
|Original Assignee
|Capiau; Carine, Petre; Jean
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (11), Non-Patent Citations (19), Referenced by (20), Classifications (15), Legal Events (3)
|External Links: USPTO, USPTO Assignment, Espacenet
This is a continuation of application Ser. No. 07/910,038, filed as PCT/EP91/00257, Feb. 7, 1991, published as WO91/12020, Aug. 22, 1991 now abandoned, which is a continuation-in-part of Ser. No. 07/479,098, filed Feb. 12, 1990 now abandoned.
The present invention relates generally to a process for detoxifying or toxoiding a toxic antigen from a selected pathogen in a form safe for use as a human vaccinal agent. More specifically, the invention provides a method for detoxifying pertussis toxin and using the resulting toxoid as a component in a vaccine for Borderella pertussis.
Whooping Cough, or pertussis, is a highly infectious disease which primarily affects children. In addition to causing respiratory complications, whooping cough may result in nerve damage and high mortality, particularly in children in low socioeconomic groups and in newborn infants without maternal anti-pertussis antibodies. The etiologic agent of pertussis is the gram negative coccobacillus Bordetella pertussis. The bacteria are believed to invade the respiratory tract and induce a toxic state which remains even after the disappearance of the bacteria.
Although world health organizations presently recommend the immunization of infants to prevent the incidence and spread of pertussis, great concern has arisen over the negative effects of various vaccine forms. The toxicity of conventional B. pertussis vaccine formulations causes side effects which vary from simple flushing to permanent neurological damage and/or death. Consequently, reduced use of conventional B. pertussis vaccines has resulted in re-explosion of the incidence of pertussis cases. The most widely used vaccine contains whole B. pertussis organisms which are inactivated after treatment at 56° C. for 30 minutes. Since the bacteria are not subjected to any detoxification treatment, any toxic substance which can withstand the elevated temperature is included in the vaccine and contributes to the occurrence of side effects. Another consequence of this type of vaccine is the formation of a broad spectrum of antibodies as a response upon administration. The sera induced by such vaccines lack high specificity and high protecting potential for use as preventive or therapeutic treatments, and have no value at all as diagnostic materials.
The most important methods for detoxifying pathogens for vaccine use are heat and chemical treatment with formaldehyde or glutaraldehyde. However, variabilities in cultivation of culture supernatant of B. pertussis allow the final composition of the microorganism to vary, and the deactivating agents, glutaraldehyde or formaldehyde, occasionally lead to aggregated materials subject to conversion to active toxic substances upon storage.
For example, U.S. Pat. No. 3,983,229 by Relyveld relates to a process for preparing vaccines by contacting a virus with glutaraldehyde at a concentration between 0.00131M to 0.0526M for between one and three hours. This process occurs at temperatures between 35° and 40° C. and the reaction may be stopped by the addition of an agent able to block glutaraldehyde or react with glutaraldehyde in its free state. The blocking agent can be an amino acid or an inorganic salt, U.S. Pat. No. 4,070,454 by Relyveld discloses another process for preparing a viral vaccine which involves inactivating the virus with glutaraldehyde at a concentration of 0.00263M for between 1.5 hours to about 5 days. U.S. Patent No. 4,075,321 further improves this process for inactivating bacterial toxins by reacting whole bacteria with glutaraldehyde at a concentration of from about 0.00131 to 0.0526M.
Gupta, J. Biol. Stand., 15:159-164 (1987) compares whole cell vaccines obtained via the classical heat treatment with those obtained via Relyveld's method of glutaraldehyde detoxification reaction. Both types of vaccine clearly lose 30 to 50% of their potency upon storage at 35° C. for 30 days. Further, these preparations have important disadvantages when compared with more recently developed acellular or component vaccines, e.g., low immunogenicity and serious side effects caused by residual toxicity upon administration. These vaccines have proven to be much less protective than those prepared from virulent strains. See Wardlaw et al, J. Med. Micro. Biol., 9:89-100 (1976).
To avoid the side effects caused by whole virus vaccines, research turned to the investigation of the toxic components of the B. pertussis bacteria for use in acellular and component vaccines. One important B. pertussis antigen is pertussis toxin (PT), a protein exotoxin which plays a major role in the pathogenesis of whooping cough and is believed to be the major protective antigen of B. pertussis [A. A. Weiss et al, Ann. Rev. Microbiol., 40:661 (1986)]. PT induces various serious biopathological changes, whether present alone or as a contaminant of other antigenic factors from this organism, at such a low amount that it impedes the administration of B. pertussis cells or cell extracts as vaccine components in amounts sufficient to provide a good level of protection. Therefore, B. pertussis cells or cell extracts must be detoxified prior to their use in a vaccine preparation.
For the detoxification of PT (or of an acellular or component vaccine mixture containing PT), three major methods have been described. In European patent application publication No. 121249A the hemagglutinin fraction, purified from a B. pertussis culture supernatant and containing PT, is detoxified with formalin in the presence of an amino acid, and subsequently used for the formulation of a vaccine. The immunogenicity and the degree of detoxification reached are excellent, but the toxicity restores partially upon storage of the vaccine preparation at 37° C. for 30 days.
Munoz, Infect. Immunol., 32:243-250 (1981) applied a detoxification method analogous to the one of Relyveld to PT, but in the presence of salt. After two hours incubation at room temperature in the presence of 0.05% glutaraldehyde, subsequent addition of lysine up to 0.02M and another two hours of incubation, and final dialysis, an anatoxin with high immunogenicity was produced. This anatoxin was stable; its toxicity did not restore after 30 days storage at 37° C.
However, the degree of detoxification was lower than obtained with the formalin/amine acid method.
In European patent application publication No. 202947A carbodiimides are presented as efficient reagents for the detoxification of PT and B. pertussis fractions containing PT. However, the toxoids obtained are not stable upon 30 day storage at 37° C.
There thus remains a continuing need in the art for effective and safe vaccines against whooping cough which retain their activity and do not revert to toxicity upon storage.
As one aspect, the present invention provides a method for the detoxification of a selected toxic antigen from a pathogenic microorganism. The method of the present invention involves the steps of partially detoxifying the selected toxin or a composition containing the toxic antigen with glutaraldehyde, followed by reacting the partially detoxified toxin with formalin in the presence of selected amino acids. The resulting toxoid or toxoid-containing preparation is stable against reversion to toxicity under the influence of temperatures above about 23° C. i.e., room temperature.
One exemplary antigen employed to illustrate the use of this method is the B. pertussis toxin. Other toxins which may be subjected to the method of this invention include, for example, tetanus toxin or diphtheria toxin. This method can be used to inactivate the toxin, e.g., pertussis toxin (PT), which is present as a primary component or only as a contaminant in preparations containing antigenic factors which are non- toxic alone, e.g., the other B. pertussis antigens FHA, 69K and agglutinogens. The method of this invention can reduce the toxicity associated with the presence of the selected toxin alone or in compositions of other antigenic factors of the same pathogen to suitable levels for use in vaccine formulations.
As another aspect, this invention provides detoxified pertussis toxin that is stable to reversion to toxicity at temperatures of 23° C. or above. This toxoid of the invention is also characterized by a high degree of immunogenicity, as is demonstrated by the ability of the toxoid to induce neutralizing antibodies. The presence of neutralizing antibody is detected by specific assays, i.e., histamine sensitization of mice or clustering of Chinese Hamster Ovary cells. The detoxified toxins of this invention are stable enough to preserve immunogenicity for more than a month under adverse storage conditions at 37° C. These toxoids are useful starting materials for the composition of high quality B. pertussis vaccines, and may also be used for mixed vaccines, or for the preparation of hyperimmune sera.
As another aspect of the present invention, there are provided compositions of B. pertussis antigenic factors, e.g., filamentous hemagglutinin (FHA), the 69K factor or other B. pertussis agglutinins, which are useful for the preparation of vaccines to the organism and which contain at least trace amounts of detoxified PT toxin as above-described.
In still a further aspect, vaccines against B. pertussis infection are provided which remain stable at temperatures of up to 56° C. and do not require special cold shipping and delivery conditions. The vaccines of this invention are characterized by easy maintenance and storage under less than optimal conditions. The vaccines developed using the toxoids of the present invention enable vaccination programs to be executed in isolated or poorly developed regions, where cold storage conditions normally required for the maintenance of other toxoided vaccines is unavailable and atmospheric conditions are extreme. Even in such conditions the vaccines of this invention are stable, and of high quality.
Still a further aspect of this invention is a method for preparing mono- or multifunctional vaccines incorporating an effective amount of the toxoids of the present invention. Other aspects and advantages of the present invention are described further in the following detailed description thereof.
The present invention provides a method for detoxifying selected pathogenic toxic antigens, e.g., B. pertussis toxin, for use in vaccine formulations, improved vaccine formulations containing the selected toxoid and the preparations containing the toxoided antigen.
It is reasonably expected that the method of the present invention is capable of toxoiding a number of toxic antigens from a variety of pathogenic microorganisms for which vaccines are desirable, e.g., tetanus toxin or diphtheria toxin, among others. However, for ease of description and experimentation, the pertussis toxin from the pathogen Borderella pertussis is employed herein to illustrate the efficacy of this toxoiding method.
Briefly described, the toxoided PT of this invention is produced by partially detoxifying the toxin using glutaraldehyde as a reagent and then reacting the PT with formaldehyde in the presence of amino acids.
According to this invention, extracts of PT are obtained from a fermentation broth or culture of Bordetella pertussis. Various strains of B. pertussis for use in the methods of this invention are described and readily available in commercial collections, such as the American Type Culture Collection, Rockville, Md. Any of these available strains may be used in the processes of the present invention, provided they are capable of producing the desired antigenic factor, PT, in adequate amounts in a liquid culture medium.
Examples of strains that may be employed in the present invention include, without limitation, B. pertussis phase I, B. pertussis phase II, B. pertussis phase I CS, B. pertussis Tohama, B. pertussis strain 185-30, B. pertussis strain 18-323, B. pertussis strain 134, B. pertussis strain 509, B. pertussis strain Wellcome 28, and Office of Biologics B. pertussis strain 165. A preferred strain for use in the present invention is B. pertussis phase I, Tohama, which is available from the Institute of Fermentation, Osaka, Japan, under accession number IFO-14073.
For use in the present invention the selected B. pertussis strain can be grown in a variety of ways known to one of skill in the art. Various cultivation methods are known which employ different cultivation steps, and liquid or solid media, depending on the quantity and origin or conservation method of the seed culture. However, any known method will suffice for use in the present invention which provides an inoculum of an conventionally acceptable size for large scale production.
A suitable medium for growth of a B. pertussis inoculum may be selected by one of skill in the art including, without limitation, Gengou medium [European patent No. 0 077 646; the media described in N. Andorn et al, Appl. Microbiol. Biotechnol., 28:356-360 (1988) and references cited therein; Verway medium [U.S. Pat. No. 4,784,589]; synthetic medium B2 [P. Van Hemert, in. Proq. Indust. Microbiol., (Bull, M. J., ed), vol. 13, p.151, Elsevier Sci., Amsterdam (1977)] or described modifications thereof.
For growth of the B. pertussis culture, which is the starting material of the present invention, an inoculum is added to a suitable liquid medium and fermentation is conducted employing conventional fermentation methods and fermentor designs known in the art. Those of skill in the art will appreciate that different results may be obtained depending upon the selection of a particular combination of conventional fermentor design, fermentation medium, method and parameters. Preferred combinations for use in the present invention are those suitable for use in large-scale production. Examples of such combinations of methods, designs and media are exemplified in European patent application publication No.A 077,646; European patent application publication No.A 121,249; European patent application publication No.A 239,504; Andorn et al, Sato et al (1983), Sekura et al and Svoboda et al, all cited above. The methods described in European patent application publication No.A 121,249; Andorn et al, cited above, and European patent application No.A 239,504 are most preferred.
In the practice of this invention, after completion of fermentation, the B. pertussis fermentation broth is maintained in a sterile condition to avoid denaturation and/or degradation of the desired PT factor. In a preferred embodiment of the invention the broth is cooled to 1°-10° C. and held at this temperature. The pH is adjusted to below 7.0. Preferably the pH is adjusted to a range of between about pH 6.0 and pH 6.4 with phosphoric or acetic acid. A preservative can optionally be added, e.g., sodium thimerosal to a final concentration of up to 0.2 g/l or 2-phenoxy-ethanol up to a final concentration of between 0.5% to 1%, to the broth. If desired, a preservative may be also added to the buffer solutions used in the processes of this invention.
As an optional first step in the method of the invention, the fermentation broth can be passed over a filter to remove major particles and pellets therefrom, provided that contact is avoided with contamination risks from the environment. The resulting broth may be subjected to the following steps of the method. Alternatively, a more purified solution containing PT may be treated by the following steps. For ease of explanation, the method will refer to an "antigenic factor solution", which is defined as a preparation containing PT and optionally other B. pertussis antigenic factors, such as FHA. This preparation can include fermentation broth containing primarily PT, or a purified solution containing primarily other B. pertussis antigens with only contaminating amounts of PT.
According to the method of this invention the antigenic factor solution is diluted to a toxin concentration of approximately 0.02 to 2 mg/ml, preferably 0.1 to 0.25 mg/ml, in an aqueous medium buffered to approximately neutral pH, i.e., pH 5 to about pH 9. Preferably the pH range is 7.5-7.7. A desirable aqueous buffer for this dilution is phosphate buffered saline (PBS). An exemplary buffer contains 50 mM phosphate and 0.5M NaCl, and is referred to herein as Buffer D.
After dilution, the solution may be optionally sterilized by filtration, e.g., through a 0.22 micron sterile membrane. The antigenic factor solution is treated with from 0.03 to 0.07% of a 25% aqueous solution of glutaraldehyde by weight. More preferably, a dilution containing 0.55% of the aqueous 25% glutaraldehyde solution is employed in this treatment step. For purposes of this step the 0.55% by weight glutaraldehyde is preferably present in the buffer D described above.
The glutaraldehyde solution is applied to the antigenic factor solution for approximately 1 to 4 hours. More preferably a range of 1 to 3 hours is employed in the glutaraldehyde treatment step, with a presently preferred time of 2 hours. The temperature of the glutaraldehyde treatment step is desirably ambient temperature, between approximately 20° C. to 25° C. Optionally, shorter reaction times can be used in combination with higher than ambient temperatures, or longer times can be used with lower than ambient temperatures. Inactivation can also be obtained at different reaction temperatures and adequately modified contact times, for example, a temperature of 10° C. may be used for 2 to 8 hours, more preferably for 4 hours. A temperature of 30° C. may be employed for 30 minutes to 2 hours, more preferably 1 hour. Alternatively a temperature of 37° C. may be used for between 15 minutes to 1 hour, more preferably 30 minutes. This glutaraldehyde treatment step may result in partial detoxification of the antigenic factor depending on the time of reaction and concentration of reagents. For example, glutaraldehyde treatment at the concentration described above for 2 hours at 20°-25° C. yields a reduction to 0.003% of the toxic activity. The other treatment conditions may result in a greater reduction of toxic activity.
After this detoxification step, at least one selected amino acid is added to the partially detoxified antigenic factor in the solution. The amino acid is added to a final concentration of approximately 0.05 to 2% by weight. Preferred concentrations of the amino acid is 0.8% by weight.
The selected am.ino acids for use in this step may include tryptophan, glycine, lysine and derivatives thereof or other amino acids such as those present in protein hydrolyzates. Preferably the amino acids are tryptophan, lysine and glycine or derivatives thereof. The amino acids are preferably prepared in solution, e.g., in the Buffer D described above and may be added to the antigenic factor solution separately or as a mixture of two or more amino acids. In one presently preferred embodiment, three solutions are prepared in Buffer D which contain, respectively, 10% (w/v) Tween® 80 solution, 33 ml of 57.4 mM N-acetyl-tryptophan and 11 ml of 2.2M glycine. These three solutions are sterilized by filtration through a 0.22 micron sterile membrane.
The formalin is added to the antigenic factor and amino acid solution in a concentration of between 1 and 10% by weight, and more preferably 2-4% by weight. The formalin may also be prepared in Buffer D or a like buffer. The formalin is added to the antigenic factor/amino acid solution in approximately equivalent amounts over a period of between 3 to 10 days, more preferably 7 days. During the formalin treatment, the toxins are maintained at a temperature of between 37° to 45° C. In a preferred embodiment the toxins are maintained at between 39° to 41° C. during this step. Preferably the toxins are also agitated periodically during this period and kept under sterile conditions. At the end of the formalin/amino acid treatment step the detoxified B. pertussis toxoid solution can be stored at low temperatures, preferably between 2°-6° C. overnight. Any aggregates formed during the detoxification process are then destroyed by subjecting the toxoid to ultrasonication. For example, the solution may be subjected to sonication at a frequency of about 16-80 KHz with a power of up to 1000 watts for a time of 1-30 seconds. Preferably the sonication involves a frequency of about 20 KHz. The range of power may more preferably be between 600-800 watts. The sonication time is preferably between 5 to 15 seconds. The resulting solution is filtered, preferably through a 50 micron screen.
As a final step in the detoxification method of this invention, the incubated product is dialyzed against PBS in a conventional manner to remove any excess reagents. Changes of the dialysis buffer and the duration of dialysis are performed a sufficient number of times to provide that the residual formalin concentration is below 200 ppm. More preferably, the formalin concentration is kept about 20 ppm. This concentration is sufficient to reduce the concentration of other agents used in the inactivation procedure to non-detectible or insignificant concentrations.
The resulting purified B. pertussis toxin or mixture of other B. pertussis antigenic factors containing PT toxoided by the method of this invention is characterized by complete and irreversible inactivation of toxicity. This stability against reversion to a toxic form is maintained even under conditions of storage in which the temperature is above room temperature, about 23° C. Such stability has been demonstrated in experimental tests for at least one week at 56° C. and for at least four weeks at 37° C. Additionally, the toxoids of the invention are expected to remain stable for more than two years at cold storage temperatures of between 4° to 8° C. This resulting toxoid or antigenic factor may then be employed as a component in B. pertussis antigen preparations which may be distributed for later preparation of vaccines or in vaccine formulations.
Therefore, this invention also provides vaccines which contain an immunoprotective quantity of the toxoids or antigenic factors of the invention, i.e., enough of the toxoided PT or other antigenic factors are administered to elicit a protective antibody response against B. pertussis infection without serious side effects. Such vaccines may be prepared by conventional techniques. For example, a vaccine for stimulating protection against B. pertussis infection in humans may contain stable toxoids and antigenic factors described above and a suitable conventional carrier. One or more of the toxoids or antigenic factors of this invention may be in an aqueous solution buffered at physiological pH for direct use. Alternatively, the toxoided antigens can be admixed or adsorbed with a conventional adjuvant, such as aluminum hydroxide or aluminum phosphate. Such a B. pertussis toxoid may also be combined with other immunogens to prepare combination or multi-functional vaccines capable of inducing protection against more than one pathogen. See, e.g., New Trends and Developments in Vaccines, eds. Voller et al, University Park Press, Baltimore, Md. (1978).
Such vaccines can be administered by an appropriate route, e.g., by the subcutaneous, intravenous or intramuscular routes. The amount of the selected toxoid of the invention present in each vaccine dose is selected by the attending physician with regard to consideration of the patient's age, weight, sex, general physical condition and the like. The amount to induce an immunoprotective response in the patient without significant adverse side effects may vary depending upon the immunogen employed and the optional presence of an adjuvant. Generally, it is expected that each dose will comprise 2 to 50 ug of antigen, preferably 5 to 25 ug each of toxoid and antigenic factor. Initial doses may be optionally followed by repeated boosts, where desirable. The following examples illustrate the methods of preparing an exemplary toxoid of the invention, and assessments of its immunogenicity and resistance to reversion to toxicity during storage. Also illustrated is an exemplary vaccine preparation employing the toxoid of this invention.
B. pertussis toxin was extracted and purified from fermentor growth cultures as described in European Patent Application Publication No. EP-A-0 352 250 which is incorporated herein by reference. One liter of the purified PT toxin was first treated at room temperature, e.g., 25° C. with 100 ml of a 0.55% (w/v) glutaraldehyde solution prepared in Buffer D. The solution is diluted to a final protein concentration of 0.2 mg/ml in Buffer D described above at neutral pH and is sterilized and filtered through a 0.22 micron sterile membrane. The glutaraldehyde treatment step is allowed to react for 2 hours. Then 4.4 ml of a 10% (w/v) Tween® 80 solution, 33 ml of 57.4 mM N-Acetyl-Tryptophan and 11 ml of 2.2M Glycine were added. These 3 solutions were prepared in the D buffer and sterilized by filtration through a 0.22 micron sterile membrane. Formalin, a 3.7% (w/v) solution in D buffer, was then added in 3 portions according to the following scheme: On the first day, 33 mls; on the second day, 33 mls; and on the third day 22 mls of formalin was added. The final formalin concentration was 0.26% (w/v). During the seven day formalin treatment, the PT toxin was maintained at 40° C.±1° C. under agitation and sterile conditions. At the end of the process, the detoxified PT bulk solution was stored overnight at 2°-6° C. before sonication. The solution was subjected to ultrasonication and the resulting antigen solution was filtered through a 50 micron screen.
The toxoid preparation of Example 1 is compared with products prepared by toxoiding with glutaraldehyde alone, with formalin and amino acids only and with glutaraldehyde and formalin/amino acids as described herein to demonstrate the advantages of the products and methods of this invention.
A study of residual toxicity of the toxoids was conducted after each sample was stored for 1 month at either 4° C. or 37° C. The study included an examination of Chinese hamster ovary (CHO) cell morphology, in which cells exposed to active PT form clusters readily distinguishable from normally growing cells by one skill in the art. See, e.g., Gillenius et al, J. Biol. Stand., 13:61-66 (1985). The test is performed by mixing serial dilutions of the toxoid or antigenic factor being tested with a suspension of 2×104 CHO cells in 200 μl culture broth in microtitre plates, allowing the cells to settle and grow at 37° C. for 2 days. At the end of the incubation, the clustering scores are recorded by microscopic examination. This test is sensitive to about 100 picograms of active toxin.
The results illustrated in TABLE 1 below show that treatment with formalin/amino acids alone yields complete inactivation, which however, is unstable and reverts to toxicity after 4 weeks at 37° C. Glutaraldehyde treatment alone yields incomplete, but stable inactivation. The process of the present invention, containing glutaraldehyde and formalin/amino acids treatment provides both complete and stable inactivation.
TABLE 1______________________________________Toxic Properties of Treated B. pertussis ToxinCHO Cells Morphology Test CPU/mcgAntigen Preparation 30 d-4° C. 30 d-37° C.______________________________________(1) Formalin-amino acids <0.009* 0.29(2) Glutaraldehyde 0.13 0.13(3) Glutaraldehyde + <0.016* <0.012* Formalin/amino acids______________________________________ *Corresponds to the detection limit of the assay. 1 CPU (cytopathic unit) is the smallest dose of antigen which induces alteration of morphology of all the cells. For native toxin, 1 CPU corresponds to a concentration of about 3 ng/ml.
The study also involved a histamine sensitization test in mice with aluminum hydroxide adsorbed vaccine. Groups of 10 mice (Swiss OF1) are inoculated intravenously with one dose of vaccine, containing 6 μg of pertussis toxoid and 25 μg of treated FHA. After 4 days, the mice are challenged intraperitoneally with 1 mg histamine in buffered saline. Two hours after challenge, the mortality rate of each group is recorded. See, e.g., Munoz et al, Infect. Immunol., 33:820-826 (1981). The histamine test is sensitive to about 30 ng active toxin/mouse.
The results of this assay are shown in TABLE 2 and demonstrate, like the CHO test, that the formalin/amino acid treatment gave complete, but reversible inactivation upon incubation of the vaccine at 37° C. for one month. However, this test failed to detect toxicity or reversion to toxicity in both the glutaraldehyde and glutaraldehyde and formalin/amino acids treated preparations. This result is not contradictory to the CHO test results, because the histamine challenge test is less sensitive than the CHO test and does not detect the residual toxicity level in the glutaraldehyde treated samples.
TABLE 2______________________________________Toxic Properties of Adsorbed B. pertussisVaccine PreparationsHistamine Sensitization Test in Mice Mortality RateAntigen Preparation 30 d-4° C. 30 d-37° C.______________________________________(1) Formalin-amino acids 0/10 6/10(2) Glutaraldehyde 0/10 0/10(3) Glutaraldehyde + 0/10 0/10 Formalin______________________________________
The toxoid preparations obtained by inactivation with formalin/amino acid treatment alone, glutaraldehyde treatment alone or the method of the present invention as described in Example 1 were tested in an enzyme immunoassay using a specific rabbit antibody directed against PT. This antibody was obtained by immunizing rabbits with toxoid inactivated by formalin/amino acids.
This antibody was conjugated to biotin to allow detection of bound antibody by a streptavidin:peroxidase reagent, by determination of absorbance at 490 nm.
The results are illustrated in TABLE 3. They show that native toxin is most efficiently recognized. Toxoid prepared by glutaraldehyde inactivation alone shows the lowest reactivity. Toxoids prepared by formalin/amino acid treatment or by the treatment of the method of this invention display an intermediate reactivity.
TABLE 3______________________________________Antigenic Properties of Toxoided PT Reactionwith Rabbit Anti-PTAntigen Preparation D at 490 nm______________________________________Native toxin 0.74Formalin/amino acids 0.39Glutaraldehyde + formalin 0.26Glutaraldehyde 0.12______________________________________
Groups of 12 mice (Balb/c).were immunized by 2 μg of the toxoid preparations given twice at 7 days interval. 14 days after the second injection, they were challenged intranasally by a hypervirulent B. pertussis strain [(18-323 Ac+); See, e.g., Brezin et al., FEMS Microbiol. Lett., 42:75-80 (1987)). Mortalities were recorded 6 days after challenge.
The results illustrated in TABLE 4 below show that the method of the invention provides a B. pertussis toxoid with the best protective efficacy.
TABLE 4______________________________________Protective Efficacy of Toxoided PT in MiceAntigen Preparation no of deaths______________________________________None 10Formalin/amino acids 4Glutaraldehyde 6Glutaraldehyde - formalin 2______________________________________
To formulate vaccines, B. pertussis antigens must be devoid of toxic properties, while retaining satisfactory immunological properties. This objective is accomplished by toxoiding B. pertussis toxin and/or by similar treatment applied to other antigens, which generally contain contaminating amounts of PT toxin. Treatment with glutaraldehyde as in U.S. Pat. No. 4,075,321 results in incomplete inactivation. Treatment with formalin alone as in European Patent Application No. 121,249 results in a complete but partially reversible inactivation and conserved immunogenicity. However, application of the method of this invention, e.g., treatment of the PT containing solution with glutaraldehyde and formalin/amino acids as herein described results surprisingly in both complete inactivation and irreversible inactivation. The resulting solution also is characterized by conserved immunogenicity. Thus, the products and processes of the present invention are valuable for their contributions to the safety and immunogenicity of B. pertussis vaccines containing these antigens.
The vaccine preparation obtained by inactivation with the method of the present invention as described in Example 1 and the preparation procedure described in Example 5 were submitted to different heating treatments: one week at 56° C., 4 weeks at 37° C. or kept for 1 year at 4°-8° C. The vaccine samples were then assayed for active PT by the histamine sensitization assay in mice as described in Example 2. The results shown in Table 5 show the absence of reversion to toxicity after the above treatments.
TABLE 5______________________________________Toxic Properties of Adsorbed B. pertussisVaccine PreparationHistamine sensitization test in micePreparation Mortalityadministered Treatment Dose rate______________________________________solvent -- 0/10native PT 0.50 μg 10/10 0.17 μg 10/10 0.05 μg 6/10vaccine none 25 μg 0/10vaccine 7 days, 56° C. 25 μg 0/10vaccine 28 days, 37° C. 25 μg 0/10vaccine 1 year, 4-8° C. 25 μg 0/10______________________________________
Antigen preparations, formulated as in example 5, were stored at 4°-8° C. and assayed at various times for the histamine sensitizing activity of PT as described in example 2 and for the ED50 of the immune response of Swiss OF1 mice to PT, i.e. the determination of the dose of inactivated PT needed to induce seroconversion of 50% of the mice. Similar tests were performed on adsorbed trivalent DTP vaccine, containing diphtheria toxoid, tetanus toxoid and the acellular pertussis vaccine components filamentous hemagglutinin and inactivated pertussis toxin prepared as described in example 1. The results (TABLE 6) show the absence of reversion and the absence of significant variations of the ED50.
TABLE 6______________________________________Immunogenicity and Stability StudiesVaccine Storage at 4-8° C. HSF test ED50Lot no (months) mortality ng/mouse______________________________________306(1) 0 0/10 42 10 0/10 <103 27 0/10 42310(1) 0 0/10 <103 10 0/10 <103 27 0/10 46353(2) 0 0/10 69 15 0/10 <103 27 0/10 58354(2) 0 0/10 50 15 0/10 152 27 0/10 80355(2) 0 0/10 76 15 0/10 <103 27 0/10 45______________________________________
(1) Inactivated PT, 25 μg.
(2) Trivalent DTP (diphtheria toxoid, tetanus toxoid, B. pertussis filamentous hemagglutinin (FHA) and inactivated PT, 25 μg).
The method of the present invention may be applied to other antigens, such as diphtheria toxin, tetanus toxin and the like. Such modifications and alterations to the compositions and processes of the present invention are intended to be encompassed in the scope of the claims appended hereto.
|Cited Patent
|Filing date
|Publication date
|Apr 30, 1974
|Sep 28, 1976
|Agence Nationale De Valorisation De La Recherche (Anvar)
|Vaccines, the process for preparing the same and the applications thereof
|Jul 12, 1976
|Jan 24, 1978
|Agence Nationale De Valorisation De La Recherche (Anvar)
|Vaccines, the process for preparing the same and the applications thereof
|Jul 12, 1976
|Feb 21, 1978
|Agence Nationale De Valorisation De La Recherche (Anvar)
|Vaccines, the process for preparing the same and the applications thereof
|May 21, 1986
|Nov 29, 1988
|The University Court Of The University Of Glasgow
|B. pertussis vaccine production using carbodiimides
|Jul 14, 1987
|Jul 18, 1989
|The Research Foundation For Microbial Diseases Of Osaka University
|Method for culturing bordetella pertussis, a pertussis toxoid and a pertussis vaccine
|Nov 9, 1988
|Dec 19, 1989
|Norden Laboratories, Inc.
|Bordetella Bronchiseptica vaccine
|Nov 28, 1989
|Feb 26, 1991
|Juridical Foundation The Chemo-Sero-Therapeutic Research Institute
|Method for preparing pertussis toxin toxoid using HcHo and amino acids
|Apr 6, 1989
|Mar 5, 1991
|Connaught Laboratories Limited
|Purification of pertussis toxins
|Dec 30, 1980
|Mar 24, 1982
|Takeda Chemical Industries, Ltd.
|Method for producing pertussis toxoid
|Mar 29, 1984
|Oct 10, 1984
|Juridical Foundation The Chemo-Sero-Therapeutic Research Institute
|Method for the production of HA fraction containing protective antigens of Bordetella pertussis and pertussis vaccine
|May 22, 1986
|Nov 26, 1986
|The University of Glasgow, University Court
|Vaccine production
|A. C. Wardlaw et al., J. med. Micro. Bio., (1976) 9, 89 100.
|A. C. Wardlaw et al., J. med. Micro. Bio., (1976) 9, 89-100.
|Andreescu et al (1980) "Comparative Studies of Pertussis Vaccine Batches Inactivated with Glutaraldehyde, β-Propiolactone, Formaldehyde or Thimerosal" Arch. Roum. Path. Exp. Microbiol. 38(3-4):299-308.
|Andreescu et al (1980) Comparative Studies of Pertussis Vaccine Batches Inactivated with Glutaraldehyde, Propiolactone, Formaldehyde or Thimerosal Arch. Roum. Path. Exp. Microbiol. 38(3 4):299 308.
|Davis et al (1974) "Retention of Significant Antibody Binding by Surface Antigens of Feline Leukemia Cells (FLA) After Fixation with Formaldehyde and Glutaraldehyde" Immunol. Commun. 3(2):189-196.
|Davis et al (1974) Retention of Significant Antibody Binding by Surface Antigens of Feline Leukemia Cells (FLA) After Fixation with Formaldehyde and Glutaraldehyde Immunol. Commun. 3(2):189 196.
|Gupta et al (1987) "The Effects of Different Inactivating Agents on the Potency, Toxicity and Stability of Pertussis Vaccine" J. Biol. Stand. 15:87-98.
|Gupta et al (1987) The Effects of Different Inactivating Agents on the Potency, Toxicity and Stability of Pertussis Vaccine J. Biol. Stand. 15:87 98.
|Habeeb (1969) "A Study of the Antigenicity of Formaldehyde-and Glutaraldehyde-Treated Bovine Serum Albumin and Ovalbumin-Bovine Serum Albumin Conjugate" J. Immunol 102(2):457-465.
|Habeeb (1969) A Study of the Antigenicity of Formaldehyde and Glutaraldehyde Treated Bovine Serum Albumin and Ovalbumin Bovine Serum Albumin Conjugate J. Immunol 102(2):457 465.
|Habeeb (1987) "Schistosoma Mansoni: Chemical Stabilization of Cercariae by Aldehydes" Exptl. Parasitol. 64:111-119.
|Habeeb (1987) Schistosoma Mansoni: Chemical Stabilization of Cercariae by Aldehydes Exptl. Parasitol. 64:111 119.
|Kongsvik et al (1974) "Studies on the Red Cell and Antibody-Reactive Sites of the Parvovirus H--1: Effect of Fixatives" Proc. Soc. Exptl. Biol. Med. 145:763-770.
|Kongsvik et al (1974) Studies on the Red Cell and Antibody Reactive Sites of the Parvovirus H 1: Effect of Fixatives Proc. Soc. Exptl. Biol. Med. 145:763 770.
|Munoz et al., Infect. Immunity, (1981) 32, 243 250.
|Munoz et al., Infect. Immunity, (1981) 32, 243-250.
|R. K. Gupta et al., J. of Biol. Stand. (1987) 15, 159 164.
|R. K. Gupta et al., J. of Biol. Stand. (1987) 15, 159-164.
|Weiss et al., Ann. Rev. Microbiol., 40:661 (1986).
|Citing Patent
|Filing date
|Publication date
|May 22, 1995
|Mar 23, 1999
|American Cyanamid Company
|Efficacious vaccines against bordetella pertussis comprising a combination of individually purified pertussis antigens
|May 22, 1995
|Mar 23, 1999
|American Cyanamid Company
|Efficacious vaccines against Bordetella pertussis comprising a combination of individually purified pertussis antigens
|May 22, 1995
|Apr 20, 1999
|American Cyanamid Company
|Efficacious vaccines against Bordetella pertussis comprising a combination of individually purified pertussis antigens
|May 22, 1995
|Apr 27, 1999
|American Cyanamid Company
|Efficacious vaccines against Bordetella pertussis comprising a combination of individually purified pertussis antigens
|Jun 8, 1999
|Sep 3, 2002
|Connaught Laboratories, Inc.
|Purification of a pertussis outer membrane protein
|Mar 13, 2003
|Nov 9, 2004
|Pfizer Inc.
|Adjuvants for use in vaccines
|Sep 29, 2004
|Jul 1, 2008
|Pfizer Inc.
|Adjuvants for use in vaccines
|May 24, 2006
|Feb 15, 2011
|Method for preparing a stable immunogenic product comprising antigenic heterocomplexes of TNFα and a carrier protein
|Apr 20, 2012
|Jul 9, 2013
|Wyeth Llc
|Compositions relating to a mutant Clostridium difficile toxin and methods thereof
|Mar 22, 2013
|Oct 15, 2013
|Wyeth Llc
|Compositions relating to a mutant Clostridium difficile toxin and methods thereof
|Aug 19, 2013
|Dec 2, 2014
|Wyeth Llc
|Compositions relating to a mutant Clostridium difficile toxin and methods thereof
|Mar 21, 2012
|Nov 3, 2015
|Altimmune Inc
|Rapid and prolonged immunologic-therapeutic
|Jul 10, 2015
|Nov 17, 2015
|Wyeth Llc
|Compositions relating to a mutant Clostridium difficile toxin and methods thereof
|Aug 7, 2013
|Feb 2, 2016
|Uab Research Foundation
|Vaccine and drug delivery by intranasal application of vector and vector extracts
|Mar 13, 2003
|Sep 18, 2003
|Roberts David S.
|Adjuvants for use in vaccines
|Mar 13, 2003
|Sep 18, 2003
|Roberts David S.
|Adjuvants for use in vaccines
|Jan 16, 2003
|Jan 15, 2004
|Tang De-Chu C.
|Vaccine and drug delivery by topical application of vectors and vector extracts
|May 24, 2006
|Aug 14, 2008
|Method for Preparing a Stable Immunogenic Product Comprising Antigenic Heterocomplexes of Tnf Alpha and a Carrier Protein
|Dec 23, 1999
|Jan 18, 2006
|Pfizer Products Inc.
|Adjuvants for use in vaccines
|Jan 15, 1999
|Jul 22, 1999
|Maxim Pharmaceuticals, Inc.
|RECOMBINANT CtB-BASED VACCINES
|U.S. Classification
|424/240.1, 424/197.11, 530/410, 530/404, 530/406, 530/405, 424/236.1, 530/403, 530/409
|International Classification
|Cooperative Classification
|European Classification
|Apr 28, 2000
|Fee payment
Year of fee payment: 4
|Mar 29, 2004
|Fee payment
Year of fee payment: 8
|Apr 17, 2008
|Fee payment
Year of fee payment: 12


text:
Michael Sykes, 19-Year-Old Suspect Wanted in Brutal Gang Rape of 11-Year-Old Girl, Could Be in L.A.
Authorities say an 11-year-old girl was gang raped in this park.
Google Maps
Updated after the jump: The teen suspect at-large was arrested this morning.
The attack shocked even veteran cops.
They say an 11-year-old girl was raped by at least 7 young gang members at a Moreno Valley park. Over the weekend Riverside County Sheriff's officials revealed that one of the suspects, 19-year-old Michael Sykes, could be in the metro L.A. area as we speak.
Six suspects, all underage, have already been arrested.
The attack at Victoriano Park in the 25700 block of Los Cabos Drive happened in a public restroom sometime before 9 p.m. on March 10. Why did it take so long for sheriff's officials to report it?
View Larger Map
Upcoming Events
Los Angeles Angels vs. Oakland Athletics
TicketsTue., Aug. 2, 7:05pm
LA Galaxy vs. New York Red Bulls
Sun., Aug. 7, 6:30pm
LA Galaxy vs. Colorado Rapids
Sat., Aug. 13, 7:30pm
Los Angeles Angels vs. Seattle Mariners
TicketsMon., Aug. 15, 7:05pm
Cops won't say, only telling the Riverside Press-Enterprise that it's not uncommon to keep such a crime under wraps for fear of mucking up an investigation.
Authorities said the six were caught immediately and booked on suspicion of sexual assault on a child. A sheriff's statement:
It is believed Sykes has since fled to the Los Angeles area, and a warrant for his arrest will be issued. All suspects involved in this investigation are suspected gang members and associates of a local street gang in Moreno Valley.
It shocks you to your core," Riverside County Sheriff Stan Sniff told the Press-Enterprise. "It never ceases to amaze me how vicious these things can be."
Anyone with information on suspect Sykes or the attack was asked to call Det. Duke Viveros at 951-247-8700.
Update: Authorities said they nabbed Sykes at a Moreno Valley home this morning, according to KTLA News.
First posted at 8:09 a.m. Monday, March 28.
Get the This Week's Top Stories Newsletter
Every week we collect the latest news, music and arts stories — along with film and food reviews and the best things to do this week — so that you'll never miss LA Weekly's biggest stories.
In Case You Missed It
Upcoming Events
Chelsea vs. Liverpool FC
TicketsWed., Jul. 27, 8:00pm
Premium Seating: Los Angeles Angels v BOSTON RED SOX
TicketsThu., Jul. 28, 7:05pm
Los Angeles Angels vs. Boston Red Sox
TicketsThu., Jul. 28, 7:05pm
Premium Seating: Los Angeles Angels v OAKLAND ATHLETICS
TicketsTue., Aug. 2, 7:05pm
Popular Stories
Sponsor Content


text:
Manufacturer Suggested Age: 12 Years and Up
Bicycle Frame Height: 18"
Bicycle Frame Material: Aluminum
Suspension Type: Front
Suspension Features: Front Suspension
Suspension Manufacturer/Type: Chitech
Seat Features: Quick Release Seat, Adjustable Seat Height
Seat Material: Vinyl
Front Brake System: Disc
Rear Brake System: Disc, V Brake
Brakes Manufacturer/Type: Chitech
Derailleur Manufacturer/Type: Shimano Index
Shifter Manufacturer/Type: Shimano TZ40
Bicycle Chain Material: Alloy, Steel
Pedal Material: Alloy
Wheel Features: Pneumatic Tires
Rim Material: Metal Alloy
Front Wheel Height: 29"
Rear Wheel Height: 29.000
Tire Type: Knobby
Tire Width: 2"
Includes: shimano derailleur, spokes, kickstand
Maximum Weight Capacity: 275.000
Care and Cleaning: Wipe Clean with Soap and Water
Dimensions: 71.000 L x 26.000 W x 29.000 H
Folded Dimensions: 71.000 L x 26.000 W x 30.000 H
Weight: 41.800
Warranty Description: Multiple Warranties and/or Time Frames Apply
Battery: no battery used:
Assembly Details: assembly required
Bike Type: Mountain
other Info.
Warranty Information
To obtain a copy of the manufacturer's warranty for this item, please call Target Guest Services at 1-800-591-3869.
- Online Item #: 13760589
- Store Item Number (DPCI): 082-09-0079
- Item can be gift wrapped.
- Imported


text:
Melrose Reservation: Photo Studio (2 hrs) Phone registration required
(Photo Studio)
Event Category: Melrose Studio Reservation
Photo Studio reservations can be made by Melrose members with Photo Studio access credentials. For more information on how to become a member of the Melrose Center, visit ocls.info/melrose. You must be present for the duration of the session and ensure that all users follow the Terms of Use (ocls.info/MelroseTerms) and Library Rules of Conduct (ocls.info/RulesOfConduct). RESERVING TIME IN THE CENTER A Cardholder can make a reservation in-person at the Center or call 407-835-7323. If a Cardholder is 15 minutes or more late to their Studio reservation time, access to the Studio will not be granted, and a $25 Late Cancellation/No Show fee will be assessed to the Cardholder's account. Any reservation must be cancelled not later than 11:59 pm three days prior to the reservation time in order to avoid the Late Cancellation fee. For instance, if a reservation was made for anytime on Friday, the cancellation must be made no later than 11:59 pm on the prior Tuesday. These same cancellation rules apply for weekend days as the Center is open 7 days. Setup, breakdown, saving of work, and clean-up times are built into, are part of, and will not extend the reservation time. The studio must be restored back to its original condition by the Cardholder before the end of the reservation time. There is no grace period. Failure to check out by the end of the reservation time will result in a $25 fee. Members and guest accessing studios, editing bays and sound booths are required to sign the Melrose Center Terms of Use. Guest accessing these spaces are also required to present state issued identification card. Please call 407.835.7381 or email firstname.lastname@example.com if you have any questions or concerns. #tic #phototicLearn more >
Lightroom for Photographers Level 2 Registration required
(Melrose Classroom)
Discover how easy it is to adjust one or multiple photos with just a few simple clicks. Quickly edit, correct exposure, convert images and enhance the color of your photos. Cut down your workflow in half the time! #tic #phototic #adobeLearn more >
SRP: Teen Voices Phone registration required
(Club Central)
Event Category: Teens
Join our teen advisory board to meet new people and develop teen library programs and services while earning community service hours. This board meets the fourth Thursday of each month. #srpteens #tweenLearn more >
Practice Makes Perfect Registration required
(Chickasaw - Combined Meeting Room)
Event Category: Library Events
Join other new English speakers for conversational English practice each Thursday at the Chickasaw Branch. A certified instructor with the Adult Literacy League, will lead and facilitate programs. Registration is required, please call 407.835.7323 to reserve your spot! This program is presented through partnership established between the Orange County Library System and the Adult Literacy League, Inc. #esolLearn more >
Basic Spanish: A language Series Registration required
(Southeast - Meeting Room 2)
Event Category: Library Events
This is a series of Spanish language workshops to help you get a basic understanding of common words and terms in Spanish. #learnalanguage #Spanish #Learn #BasicspanishLearn more >
Microsoft Excel 2013: Pivot Tables Registration required
Learn how to create Pivot Tables and Pivot Charts to organize and manipulate data. Recommended Audience: Adult #officetrainingLearn more >
Microsoft Excel 2013: Data Management I Registration required
(Chickasaw - Technology Classroom)
Learn how to use advanced sort and filter options; apply data validation and other data tools to organize your data. Recommended Audience: Adult #officetraining #pcenLearn more >
QuickBooks Pro 2015 Level 2 Registration required
(Washington Park - Ask At Desk)
Learn how to setup a new company profile including the Vendor Center, Customer Center and adding Items. Recommended Audience: Adult #officetrainingLearn more >
Microsoft Excel 2013: Formulas and Functions Registration required
(Herndon - Training Lab)
Learn how to create formulas and insert advanced functions. Become familiar with the Function Library to assist with finding functions and inserting function arguments. Recommended Audience: Adult #officetrainingLearn more >
Open Lab: Ask A Tech Registration required
(Edgewater - Computer Area)
Event Category: Open Lab: Ask a Tech
Are you stuck on a software-related project or simply need constructive ideas to get you started? Let us help! A technology trainer will be available to assist you in this open lab. Please note: Software questions are handled based on the topics discussed in any of the classes offered at the Library. Recommended Audience: AdultLearn more >
Filter search Hide filters
- Alafaya Branch (360) Apply Alafaya Branch filter
- Chickasaw Branch (383) Apply Chickasaw Branch filter
- Eatonville Branch (62) Apply Eatonville Branch filter
- Edgewater Branch (161) Apply Edgewater Branch filter
- Herndon Branch (412) Apply Herndon Branch filter
- Hiawassee Branch (161) Apply Hiawassee Branch filter
- Melrose Center (794) Apply Melrose Center filter
- North Orange Branch (226) Apply North Orange Branch filter
- Online (33) Apply Online filter
- Orange County Library System - All Locations (13) Apply Orange County Library System - All Locations filter
- Orlando Public Library (499) Apply Orlando Public Library filter
- South Creek Branch (434) Apply South Creek Branch filter
- South Trail Branch (242) Apply South Trail Branch filter
- Southeast Branch (573) Apply Southeast Branch filter
- Southwest Branch (213) Apply Southwest Branch filter
- Washington Park Branch (254) Apply Washington Park Branch filter
- West Oaks Branch (240) Apply West Oaks Branch filter
- Windermere Branch (257) Apply Windermere Branch filter
- Winter Garden Branch (318) Apply Winter Garden Branch filter
- Art Display/Exhibit (1) Apply Art Display/Exhibit filter
- Arts & Cultural (27) Apply Arts & Cultural filter
- Books & Authors (8) Apply Books & Authors filter
- Children (1781) Apply Children filter
- Health (1) Apply Health filter
- Holiday/Closings (13) Apply Holiday/Closings filter
- Library Board Meetings (1) Apply Library Board Meetings filter
- Library Events (972) Apply Library Events filter
- Live Online Class (36) Apply Live Online Class filter
- Melrose Studio Reservation (136) Apply Melrose Studio Reservation filter
- Music in the Library (11) Apply Music in the Library filter
- Open Lab: Ask a Tech (62) Apply Open Lab: Ask a Tech filter
- Open Language Lab (291) Apply Open Language Lab filter
- Technology Classes (2201) Apply Technology Classes filter
- Teens (90) Apply Teens filter
- Adults (2930) Apply Adults filter
- All Ages (438) Apply All Ages filter
- Babies (416) Apply Babies filter
- Families (149) Apply Families filter
- Kids (745) Apply Kids filter
- Preschoolers (519) Apply Preschoolers filter
- Seniors (69) Apply Seniors filter
- Teens (613) Apply Teens filter
- Toddlers (591) Apply Toddlers filter
- Tweens (642) Apply Tweens filter


text:
(This story first ran at PressConnects.com) BALTIMORE — At 26 years old, UFC light-heavyweight champion Jon Jones admits it is difficult even for him to realize he could soon be considered the best fighter in the history of mixed martial arts. But it's a reality (…)
Watch the Bellator 159: Caldwell vs. Taimanglo preliminary bouts LIVE STREAM on MMAWeekly.com on Friday at 6:45 p.m. ET. read news >>
Bantamweights Eddie Wineland and Frankie Saenz headlined the UFC on Fox 20 preliminary card in Chicago on Saturday. Check out the fight highlights. read news >>


text:
This research was supported by NIH-NRSA Grant F32HD063255 awarded to Saxbe and by NIH-NICHD Grant R01 HD046807 and the David and Lucile Packard Foundation Grant 00-12802 awarded to Margolin. We thank the families who participated in the study and other members of the USC Family Studies Project.
Does Dampened Physiological Reactivity Protect Youth in Aggressive Family Environments?
Version of Record online: 30 MAR 2012
DOI: 10.1111/j.1467-8624.2012.01752.x
© 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.
Child Development
Volume 83, Issue 3, pages 821–830, May/June 2012
Additional Information
How to Cite
Saxbe, D. E., Margolin, G., Spies Shapiro, L. A. and Baucom, B. R. (2012), Does Dampened Physiological Reactivity Protect Youth in Aggressive Family Environments?. Child Development, 83: 821–830. doi: 10.1111/j.1467-8624.2012.01752.x
Publication History
- Issue online: 1 MAY 2012
- Version of Record online: 30 MAR 2012
Options for accessing this content:
- If you are a society or association member and require assistance with obtaining online access instructions please contact our Journal Customer Services team.
- If your institution does not currently subscribe to this content, please recommend the title to your librarian.
- Login via other institutional login options http://onlinelibrary.wiley.com/login-options.
- You can purchase online access to this Article for a 24-hour period (price varies by title)
- If you already have a Wiley Online Library or Wiley InterScience user account: login above and proceed to purchase the article.
- New Users: Please register, then proceed to purchase the article.
Login via OpenAthens
Search for your institution's name below to login via Shibboleth.
Registered Users please login:
- Access your saved publications, articles and searches
- Manage your email alerts, orders and subscriptions
- Change your contact information, including your password
Please register to:
- Save publications, articles and searches
- Get email alerts
- Get all the benefits mentioned below!
Patient Access
Patients and/or caregivers may access this content for use in relation to their own personal healthcare or that of a family member only. Terms and conditions will apply.


text:
From broad liability insurance to the profession's best Continuing Education, AMTA membership provides the tools you need to thrive in your massage therapy career. Sign in to view your benefits »
Join AMTA »
Explore the profession's best education, both face-to-face and online. Expand your knowledge and take your career to the next level.
Access Continuing Education »
Learn tips to integrate body, mind and spirit in this online course.
Take this course now »
From SOAP notes to intake forms, use these tools to market your practice, expand your business and make informed decisions about your professional growth.
Explore Career Guidance »
Search massage therapy jobs in your area or find qualified candidates with ease. AMTA members post open positions and resumes for free.
AMTA Job Bank »
A growing body of research supports the health benefits of massage therapy. Educate your clients with our resources.
Get the research »
Stay engaged with timely massage therapy news and updates through our award-winning publications and related news stories.
Be in the Know »
A growing body of research supports massage therapy for health and wellness. Use research to explain the health benefits of massage to your clients, and reference our research on the profession's growth in business planning. Let AMTA empower your practice with evidence and information.
A growing body of research is documenting the impact of massage therapy for relief of anxiety and depression. Review the research »
Recent studies show massage therapy can reduce pain, stress, nausea, depression, distress, anxiety and fatigue, while improving health related quality of life for cancer patients. Review the research »
More Current Research >>
AMTA conducts extensive annual research on consumer behavior, employment trends and other factors influencing the massage therapy profession.
Consumer Survey Fact Sheet »Massage Profession Research Report »Industry Survey Fact Sheet »
Looking for specific massage therapy practice information? Contact AMTA for custom research services on massage therapy topics.
AMTA is the primary benefactor of the Massage Therapy Foundation, helping MTF carry out its mission and reinforcing AMTA's goal of evidence-informed massage practice.
"Being a member of AMTA has totally opened my business and career wide open."
—Kelly L., AMTA member since 2010
AMTA has long been the leading choice among massage therapists looking to establish themselves within the profession. We provide our members with the strongest benefits and promote massage therapy to the public and health care community.
Learn more
Read mtj »


text:
Caribou Café1126 Walnut St | 215.625.9535Reserve Now!
First Course
Smoked salmon Rillettes, brioche and arugula salad
Second Course
(choice of one)
Coq au vin
Seafood Crêpe
Third Course
Today's pot de crème
Produced By:
Sponsored By:
Keep up on the latest news about Center City District Restaurant Week, by following our official Twitter feed!
Everything you need for CCD Restaurant Week, right on your phone! M.CENTERCITYPHILA.ORG»


text:
by amandab 7/19/2016 10:29:14 AM --
WEST POINT - Northeast Community College in West Point will host an open house in August to spotlight the various programs it offers. The Adult Education Open House will be held Wednesday, August 10, from 2-4 p.m. at Northeast's West Point extended campus, 202 Anna Stalp Avenue.
by jamesc 7/14/2016 4:08:23 PM --
NORFOLK – Northeast Community College has selected Amanda Nipp as its new vice president of student services. Nipp, who currently serves as the College's dean of enrollment management, will assume the new position on July 18.
by jamesc 7/14/2016 4:06:31 PM --
NORFOLK – The Northeast Community Board of Governors approved the institution's new five-year strategic plan a year ago. At its monthly meeting here Thursday, College administrators provided the board with an update on first year accomplishments through Vision 2020.
by jamesc 6/27/2016 10:12:05 AM --
NORFOLK - In observance of Independence Day, all offices at Northeast Community College in Norfolk and its extended campuses in O'Neill, South Sioux City and West Point, will close on Friday, July 1, at 3 p.m. The college and its extended campuses will re-open Tuesday, July 5, at 8 a.m.
by jamesc 6/24/2016 8:57:30 AM --
NORFOLK – Susan Risinger Green has joined Northeast Community College to serve as the campaign coordinator for its proposed Agriculture, Water and Energy Center of Excellence. She joins the College after more than 27 years at WJAG, Lite Rock 97.5 and 106KIX Radio in Norfolk, where she served as assistant news director and farm director.
by jamesc 6/21/2016 3:32:35 PM --
NORFOLK – Fifteen Northeast Community College student-athletes have earned academic honors through the National Junior College Athletic Association (NJCAA).
by jamesc 6/16/2016 8:30:10 AM --
KEARNEY – Dr. Michael Chipps, president of Northeast Community College was recently named the recipient of Nebraska's prestigious Elaine Stuhr Leadership and Advocacy Award. He received the award during the Department of Education's 2016 Nebraska Career Education (NCE) Conference here. More than 600 Nebraska Career Education teachers, school counselors and administrators attended the conference.
by amandab 6/16/2016 8:03:14 AM --
WEST POINT – Constituents may be most familiar with Northeast Community College's main campus in Norfolk. However, the College also operates three extended campuses to serve those residents who live in the other areas across the 20 county service area.
by jamesc 6/15/2016 9:17:56 AM --
Terry Ramig, director of Northeast Community College's Extended Campus in West Point, visits with Board of Governors member Gene Willers, Pilger, during a reception held in her honor.
by jamesc 6/10/2016 10:46:14 AM --
WEST POINT – The Northeast Community College Board of Governors is seeking qualified applicants to fill an unexpired term on the Board.
by amandab 5/27/2016 8:01:54 AM --
NORFOLK - Officials at Northeast Community College in Norfolk have released the President's Honor List and Deans' Honor List for both full and part-time students for the Spring 2016 Semester.
by jamesc 5/20/2016 8:29:29 AM --
NORFOLK – Sixty-five associate degree nursing and practical nursing students received their nursing pins during a special ceremony recently at Northeast Community College in Norfolk. During the ceremony, the graduating nursing students received their pin from family members or a close friend who has helped them along their journey.
by jamesc 5/14/2016 1:11:34 PM --
Lacy Lawson, Norfolk, receives her Associate of Science degree from Dr. Michael Chipps, president, during Northeast Community College's 43rd Commencement Ceremony on Saturday in the Cox Activities Center on the Norfolk campus.
by jamesc 5/12/2016 5:29:55 PM --
NORFOLK - A longtime member of the Northeast Community College Board of Governors has announced he is leaving the board. Larry Poessnecker submitted his letter of resignation during the board's monthly meeting in Norfolk on Thursday.
by jamesc 5/12/2016 5:26:42 PM --
SAN DIEGO, CA – In 2013, Derek Bierman, vice president, and his staff in the Technology Services Division at Northeast Community College began working on a concept to improve technology-based customer service across the college community. Three years later, the work is being recognized on a national level.
Northeast Community College, 801 East Benjamin Ave, Norfolk,
Nebraska 68701
phone: 402-371-2020 | tollfree: 1-800-348-9033 | email:


text:
No stories have been written yet.
Games You May Like
- Racing
- digiBLAST
In Truckz you take the wheel of one of the featured massive trucks in the game and compete in tournaments around the world.
This one-on-one beat 'em up game is the third in the Gormiti series, but it deviates significantly from the previous two games.
Sparkblast is a fast-paced space shooter game. Blast your way through eight galaxies, flodded with hundreds of relentless alien enemy ships.


text:
Forgot Password? | Not a User? Sign up
Your browser does not support iframes.
By Tim Reynolds
AP Sports Writer
LONDON — Red, white and blue was everywhere in London.
For the Americans — and for the British, too.
The most medals, and the most gold medals. That's what the U.S. Olympic Team wanted, and it's what they delivered. As for the home team? Riding the wave of home-field advantage, the British put together their best Olympic showing in over a century.
The competition is over. The U.S. was best, but the success stories from London truly spanned the globe.
By Tim Dahlberg
AP Sports Columnist
LONDON — IOC President Jacques Rogge still can't figure out what to call Usain Bolt, so here's hoping he gets another Olympics to sort it out. There's just something about his latest effort —"active performance legend" — that doesn't rise to a gold medal level.
There's a lot of things we can call the London Olympics, and still not run out of superlatives. The backdrops were gorgeous, the performances spectacular and the hometown fans like no others.
The Associated Press
LONDON — This time, Usain Bolt ran hard right to the finish.
Leaned at the line, even.
Having built a big lead on the 4x100-meter relay anchor leg, Bolt knew he was about to earn his third gold medal in three events at the London Olympics.
First day of official practice for most fall high school sports programs in New Mexico was Monday, Aug. 6. Check with school coaches or athletic directors for more information.
Memorial Middle School football practice began Monday, Aug. 6, at the MMS field. Athletes must have a current physical to practice; bring form on first day of practice or you will not be able to participate. If you have any questions, please contact Coach Martinez at 429-7975.
Submitted to the Optic
The New Mexico Dream Killers have done it again — bringing back a trophy from Albuquerque.
The Dream Killers, a traveling youth soccer team based in Las Vegas, played July 28-29 at the Chivas Cup sponsored by the Guadalajara Soccer Association of New Mexico.
In its toughest competition to date the Dream Killers met up with the host team Chivas for the championship, with Chivas prevailing 4-2 after a back-and-forth game.
LONDON — With one day of competition left at the London Games, the United States had locked up the overall medal race and is holding off the Chinese in the chase for the most gold.
It will be the fifth straight Summer Games where U.S. athletes took home more prizes than anyone else from an Olympics.
Swimming, track and field, basketball, women's soccer, Serena Williams and gymnast Aly Raisman have all been highlights for U.S. Olympic Committee chairman Larry Probst.
LONDON — Now that Kobe Bryant, strangely missing, has finally joined the fun, the U.S. appears complete.
Oh, there are some major defensive flaws, but that hardly matters to this suped-up, American-manufactured scoring machine that goes from zero to 100 points in seconds.
Overpowering and dominant in a way not seen since the 1992 Dream Team, the Americans are now two wins from a second straight Olympic gold medal.
Argentina awaits.
"We're ready," Carmelo Anthony said.
LONDON — For 11 years, they have been Kerri and Misty, the most recognizable faces in Olympic beach volleyball and a team that dominated the sport.
No one could beat them in the Summer Games.
And no one will get another chance.
For Ira Harge Jr., the wheels started turning when he and fiancee Lisa Lujan were sitting courtside at a Monte del Sol basketball game.
Omar Ndiaye, a player on the school's junior varsity, caught Harge's attention for the way he handled the ball. As it turns out, Ndiaye has been playing with one hand, lacking the use of his right hand, but managed to emerge as a standout guard for the Dragons.
The encounter made Harge think.
So, too, did his meeting Dulce's Kyle Howe, who has overcome a seizure disorder to compete in athletics.
An estimated 68 area youngsters participated in the recent Coop Life Skills clinic at Robertson's Mike Marr Gym.
"Everyone left satisfied," said Arturo Padilla Jr., who helped facilitate the two-day camp that included basketball instruction and life lessons as presented by Michael Cooper Jr. and his staff.
Fifteen kids were sponsored by Collins Dental, which purchased passes for those kids who would not otherwise be able to attend. Those passes were given away on KFUN radio Thursday morning before the camp.
Copyright © 2016
The Las Vegas Optic is your source for local news, sports, events, and information in San Miguel County and Las Vegas, NM, and the surrounding area.